Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Won Hee Lee, Wen Yi Chen, Ning Yi Shao, Dan Xiao, Xulei Qin, Natalie Baker, Hye Ryeong Bae, Tzu Tang Wei, Yongjun Wang, Praveen Shukla, Haodi Wu, Kazuki Kodo, Sang Ging Ong, Joseph C. Wu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.

Original languageEnglish
JournalStem Cells
DOIs
Publication statusAccepted/In press - 2017
Externally publishedYes

Fingerprint

Exosome Multienzyme Ribonuclease Complex
Induced Pluripotent Stem Cells
Untranslated RNA
Cardiac Myocytes
Embryonic Stem Cells
Long Noncoding RNA
MicroRNAs
Myocardial Infarction
Nude Rats
Gene Expression
Fetal Heart
Sarcomeres
Troponin T
Cell Transplantation
Heart Transplantation
Human Embryonic Stem Cells
Flow Cytometry
Therapeutics
Transplantation
Calcium

Keywords

  • Cell therapy
  • Embryonic stem cell-derived cardiomyocyte
  • Exosomes
  • Induced pluripotent stem cell-derived cardiomyocyte
  • Stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes. / Lee, Won Hee; Chen, Wen Yi; Shao, Ning Yi; Xiao, Dan; Qin, Xulei; Baker, Natalie; Bae, Hye Ryeong; Wei, Tzu Tang; Wang, Yongjun; Shukla, Praveen; Wu, Haodi; Kodo, Kazuki; Ong, Sang Ging; Wu, Joseph C.

In: Stem Cells, 2017.

Research output: Contribution to journalArticle

Lee, Won Hee ; Chen, Wen Yi ; Shao, Ning Yi ; Xiao, Dan ; Qin, Xulei ; Baker, Natalie ; Bae, Hye Ryeong ; Wei, Tzu Tang ; Wang, Yongjun ; Shukla, Praveen ; Wu, Haodi ; Kodo, Kazuki ; Ong, Sang Ging ; Wu, Joseph C. / Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes. In: Stem Cells. 2017.
@article{f8ea8d4ab9984d458d59ac62450a6a2b,
title = "Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes",
abstract = "Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85{\%} and ∼83{\%} of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.",
keywords = "Cell therapy, Embryonic stem cell-derived cardiomyocyte, Exosomes, Induced pluripotent stem cell-derived cardiomyocyte, Stem cells",
author = "Lee, {Won Hee} and Chen, {Wen Yi} and Shao, {Ning Yi} and Dan Xiao and Xulei Qin and Natalie Baker and Bae, {Hye Ryeong} and Wei, {Tzu Tang} and Yongjun Wang and Praveen Shukla and Haodi Wu and Kazuki Kodo and Ong, {Sang Ging} and Wu, {Joseph C.}",
year = "2017",
doi = "10.1002/stem.2669",
language = "English",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes

AU - Lee, Won Hee

AU - Chen, Wen Yi

AU - Shao, Ning Yi

AU - Xiao, Dan

AU - Qin, Xulei

AU - Baker, Natalie

AU - Bae, Hye Ryeong

AU - Wei, Tzu Tang

AU - Wang, Yongjun

AU - Shukla, Praveen

AU - Wu, Haodi

AU - Kodo, Kazuki

AU - Ong, Sang Ging

AU - Wu, Joseph C.

PY - 2017

Y1 - 2017

N2 - Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.

AB - Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future.

KW - Cell therapy

KW - Embryonic stem cell-derived cardiomyocyte

KW - Exosomes

KW - Induced pluripotent stem cell-derived cardiomyocyte

KW - Stem cells

UR - http://www.scopus.com/inward/record.url?scp=85026475074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026475074&partnerID=8YFLogxK

U2 - 10.1002/stem.2669

DO - 10.1002/stem.2669

M3 - Article

C2 - 28710827

AN - SCOPUS:85026475074

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

ER -